SMRTER, a Drosophila nuclear receptor coregulator, reveals that EcR-mediated repression is critical for development

Mol Cell. 1999 Aug;4(2):175-86. doi: 10.1016/s1097-2765(00)80365-2.

Abstract

The Drosophila ecdysone receptor (EcR)/ultraspiracle (USP) heterodimer is a key regulator in molting and metamorphoric processes, activating and repressing transcription in a sequence-specific manner. Here, we report the isolation of an EcR-interacting protein, SMRTER, which is structurally divergent but functionally similar to the vertebrate nuclear corepressors SMRT and N-CoR. SMRTER mediates repression by interacting with Sin3A, a repressor known to form a complex with the histone deacetylase Rpd3/HDAC. Importantly, we identify an EcR mutant allele that fails to bind SMRTER and is characterized by developmental defects and lethality. Together, these results reveal a novel nuclear receptor cofactor that exhibits evolutionary conservation in the mechanism to achieve repression and demonstrate the essential role of repression in hormone signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biological Evolution
  • Cell Line
  • Chromosome Mapping
  • Chromosomes / genetics
  • Chromosomes / ultrastructure
  • Co-Repressor Proteins
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Drosophila Proteins*
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / physiology*
  • Female
  • Genetic Variation
  • Male
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry
  • Nuclear Receptor Co-Repressor 1
  • Nuclear Receptor Co-Repressor 2
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Receptors, Steroid / physiology*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Repressor Proteins / chemistry
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transfection
  • Vertebrates

Substances

  • Co-Repressor Proteins
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Nuclear Proteins
  • Nuclear Receptor Co-Repressor 1
  • Nuclear Receptor Co-Repressor 2
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Recombinant Proteins
  • Repressor Proteins
  • Smr protein, Drosophila
  • ecdysone receptor

Associated data

  • GENBANK/AF175223